Loss of Malignancy of Super-Methotrexate-resistant Osteosarcoma Cells Is Associated With an Increase of Methylated Histone Marks H3K9me3 and H3K27me3.

IF 1.6 4区医学 Q4 ONCOLOGY Anticancer research Pub Date : 2024-10-01 DOI:10.21873/anticanres.17251

Yusuke Aoki, Yutaro Kubota, Noriyuki Masaki, Koya Obara, Yasunori Tome, Michael Bouvet, Kotaro Nishida, Robert M Hoffman

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Abstract

Background/aim: Methotrexate (MTX) resistance in osteosarcoma results in a very poor patient prognosis. We previously reported that super MTX-resistant osteosarcoma (143B-MTX^SR) cells, selected from parental 143B osteosarcoma (143B-P) cells by culturing them with increasing concentrations of MTX, exhibited reduced malignancy, despite the over-expression of oncogenes. The present study explored the mechanism of reduced malignancy in the super MTX-resistant osteosarcoma cells.

Materials and methods: Previously selected 143B-MTX^SR cells which are 5,500 times more MTX resistant than parental cells, were used for this study. The status of methylated histone H3K9me3 and H3K27me3 marks was examined with western immunoblotting and compared between 143B-MTX^SR and parental 143B-P cells.

Results: Histone H3K9me3 and H3K27me3 marks were over-expressed in 143B-MTX^SR compared to 143B-P (p<0.05, p<0.01, respectively).

Conclusion: Over-expression of histone H3K9me3 and H3K27me3 marks may be related to super-MTX resistance and to the loss of malignancy of super MTX-resistant osteosarcoma cells due to the fundamental relationship of methylation and cancer.

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超级甲氨蝶呤耐药骨肉瘤细胞的恶性度丧失与甲基化组蛋白标记 H3K9me3 和 H3K27me3 的增加有关。

背景/目的：骨肉瘤中的甲氨蝶呤（MTX）耐药性会导致患者预后极差。我们以前曾报道过，超级 MTX 抗性骨肉瘤（143B-MTXSR）细胞是从亲代 143B 骨肉瘤（143B-P）细胞中筛选出来的，通过用浓度不断增加的 MTX 培养，尽管癌基因过度表达，但恶性程度却有所降低。本研究探讨了超级 MTX 抗性骨肉瘤细胞恶性程度降低的机制：本研究使用了之前筛选出的 143B-MTXSR 细胞，其 MTX 耐药性是亲代细胞的 5,500 倍。用 Western 免疫印迹法检测甲基化组蛋白 H3K9me3 和 H3K27me3 标记的状态，并比较 143B-MTXSR 和亲本 143B-P 细胞：结果：与143B-P相比，组蛋白H3K9me3和H3K27me3标记在143B-MTXSR中过度表达（p结论：组蛋白H3K9me3和H3K27me3标记在143B-MTXSR中过度表达：组蛋白H3K9me3和H3K27me3标记的过度表达可能与超MTX耐药有关，并且由于甲基化与癌症的基本关系，超MTX耐药骨肉瘤细胞的恶性度下降也与超MTX耐药有关。

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来源期刊

Anticancer research 医学-肿瘤学

CiteScore

3.70

自引率

10.00%

发文量

566

审稿时长

2 months

期刊介绍： ANTICANCER RESEARCH is an independent international peer-reviewed journal devoted to the rapid publication of high quality original articles and reviews on all aspects of experimental and clinical oncology. Prompt evaluation of all submitted articles in confidence and rapid publication within 1-2 months of acceptance are guaranteed. ANTICANCER RESEARCH was established in 1981 and is published monthly (bimonthly until the end of 2008). Each annual volume contains twelve issues and index. Each issue may be divided into three parts (A: Reviews, B: Experimental studies, and C: Clinical and Epidemiological studies). Special issues, presenting the proceedings of meetings or groups of papers on topics of significant progress, will also be included in each volume. There is no limitation to the number of pages per issue.